Inositol 1,4,5-trisphosphate (IP3) induced rapid formation of thromboxane B2 in saponin-permeabilised human platelets: mechanism of IP3 action

The mechanism of IP3-induced activation of saponin-permeabilised platelets has been examined. Saponin permeabilization resulted in the leakage of low-Mr substances into and from the cells without loss of cytoplasmic proteins. Addition of IP3 rapidly induced a dose-related formation of thromboxane B2 and release into the medium, leading to the responses of shape change, aggregation and [14C]5HT release. These responses were inhibited by the thromboxane A2 receptor antagonist AH23848. The IP3-induced release of 45Ca from intracellular stores was not affected by indomethacin. Synthesis of thromboxane was inhibited if Ca2+ elevation was prevented by using Ca-EGTA buffers during permeabilization. These studies indicate that IP3-induced activation was due to Ca2+ mobilisation leading to phospholipase activation and thromboxane synthesis.     

Transcriptional profiling of the nucleus pulposus: say yes to notochord

This editorial addresses the debate concerning the origin of adult nucleus pulposus cells in the light of profiling studies by Minogue and colleagues. In their report of several marker genes that distinguish nucleus pulposus cells from other related cell types, the authors provide novel insights into the notochordal nature of the former. Together with recently published work, their work lends support to the view that all cells present within the nucleus pulposus are derived from the notochord. Hence, the choice of an animal model for disc research should be based on considerations other than the cell loss and replacement by non-notochordal cells.     

Immunologic effects of interleukin 2 in primary immunodeficiency diseases

Five children with primary deficiencies of T cell function were studied to assess the effects of highly purified exogenous Interleukin 2 (IL 2) on their in vitro T cell responses. The lymphocytes from one child with Nezelof's T cell deficiency demonstrated absence of endogenous IL 2 production and improved proliferative responses to mitogen or alloantigen in the presence of exogenous IL 2. Moreover, during in vitro mixed lymphocyte culture in the presence of exogenous IL 2, his lymphocytes were able to develop into cytotoxic effector cells. A second child with Nezelof's syndrome demonstrated a different type of defect. The lymphocytes from this child had less impairment of endogenous IL 2 production. Although IL 2 increased the proliferation of his cells in response to PHA, similar augmentation was not seen after stimulation with OKT3 or alloantigen. In cell-mediated cytotoxicity assays, after mixed lymphocyte culture, natural killer-like activity was strongly boosted in the cultures that contained IL 2, but T cell-mediated cytotoxicity was not. The lymphocytes from three patients with severe combined immunodeficiency did not show improved proliferative responses in the presence of IL 2. Thus, only one of the five patients demonstrated the combination of defective endogenous IL 2 production, but preservation of the ability to respond appropriately to exogenous IL 2. This child may therefore have suffered from a T cell defect pathophysiologically similar to that seen in nude or aged mice.     

Comparison of factor IX methylation on human active and inactive X chromosomes: implications for X inactivation and transcription of tissue-specific genes.

Maintenance of dosage compensation for housekeeping genes on the human X chromosome is mediated through differential methylation of clustered CpG nucleotides associated with these genes. To determine if methylation has a role in maintaining inactivity of X-linked genes which show tissue-specific expression, we examined the locus for blood clotting Factor IX. The analysis encompassed 91% of the HpaII and HhaI sites in the 41-kb region that includes the presumed promoter region, 5 kb of 5'- and 4 kb of 3'-flanking sequences. Although there are sex differences in methylation of the locus in leukocytes, the methylation pattern in liver, where the gene is expressed, is essentially the same for loci on the active and inactive X chromosome. The lack of differences in methylation of active and inactive genes makes it unlikely that methylation within the locus has a role in expression of the Factor IX gene. These findings, along with the absence of clustered CpG dinucleotides within the Factor IX locus, suggest that functional differences in DNA methylation related to X chromosome dosage compensation may be limited to CpG clusters. In any event, dosage compensation seems to be maintained regionally, rather than locus by locus.     

Keratinophilic fungi from Orissa, India, II: Isolations from feathers of wild birds and domestic fowls

Feather samples from 117 birds, representing 11 species, were examined for keratinophilic fungi. Of these, 63 (53.8%) were found to be positive. Nine species of fungi classified in 6 genera were isolated: Aphanoascus terreus (1.7%), Chrysosporium indicum (26.4%), Chrys. tropicum (11.1%) the Chrysosporium state of Aphanoascus spp. (2.5%), the Chrysosporium state of Arthroderma tuberculatum (3.4%), Ctenomyces serratus (0.8%), Gymnoascoideus petalosporus (7.6%), Malbranchea spp. (6.8%), Rollandina hyalinospora (6.8%). Passer domesticus (the house sparrow) harboured the largest varieties of keratinophilic fungi: the Chrysosporium state of Arthroderma tuberculatum was found to be associated with it selectively. The associations of these keratinophilic fungi with birds were non-clinical in nature.